Background: Frailty may modify the risk-benefit profile of certain treatments, and
frail patients may have reduced tolerance to treatments. Objective: To investigate
the efficacy of dapagliflozin according to frailty status, using the Rockwood cumulative
deficit approach, in DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in
Heart Failure). Design: Post hoc analysis of a phase 3 randomized clinical trial.
(ClinicalTrials.gov: NCT03036124) Setting: 410 sites in 20 countries. Patients: Patients
with symptomatic heart failure (HF) with a left ventricular ejection fraction of 40%
or less and elevated natriuretic peptide. Intervention: Addition of once-daily 10
mg of dapagliflozin or placebo to guideline-recommended therapy. Measurements: The
primary outcome was worsening HF or cardiovascular death. Results: Of the 4744 patients
randomly assigned in DAPAHF, a frailty index (FI) was calculable in 4742. In total,
2392 patients (50.4%) were in FI class 1 (FI <= 0.210; not frail), 1606 (33.9%) in
FI class 2 (FI 0.211 to 0.310; more frail), and 744 (15.7%) in FI class 3 (FI >= 0.311;
most frail). The median follow-up time was 18.2 months. Dapagliflozin reduced the
risk for worsening HF or cardiovascular death, regardless of FI class. The differences
in event rate per 100 person-years for dapagliflozin versus placebo from lowest to
highest FI class were-3.5 (95% CI,-5.7 to-1.2),-3.6 (CI,-6.6 to-0.5), and-7.9 (CI,-13.9
to-1.9). Consistent benefits were observed for other clinical events and health status,
but the absolute reductions were generally larger in the most frail patients. Study
drug discontinuation and serious adverse events were not more frequent with dapagliflozin
than placebo, regardless of FI class. Limitation: Enrollment criteria precluded the
inclusion of very high-risk patients. Conclusion: Dapagliflozin improved all outcomes
examined, regardless of frailty status. However, the absolute reductions were larger
in more frail patients. Primary Funding Source: AstraZeneca. Ann Intern Med. doi:10.7326/M21-4776
Annals.org For author, article, and disclosure information, see end of text. This
article was published at Annals.org on 26 April 2022.
